Tumor cells (cancer cells) have a higher proliferation rate than that of normal cells. When the effect of killing tumor cells is equivalent to or lower than the proliferation rate of the tumor cells, it can only suppress progression of the cancer, and thus it cannot constitute a radical cancer treatment. In addition, each antitumor agent has its own optimal dosage. Even if an antitumor agent is administered at an amount larger than such optimal dosage, the effect of killing tumor cells does not proportionally increase, but in general, the effect increases by only a slight extent. Moreover, when a large amount of antitumor agent is administered, adverse effects such as damage to normal cells appear rather strongly in many cases. Thus, it is hardly anticipated that a great therapeutic effect can be obtained by administration of a single type of antitumor agent in large amounts.
Under the aforementioned circumstances, in order to improve antitumor effects and reduce side effects, or in order to prevent tumor cells from obtaining resistance to drugs, multi-drug combination therapy in which two or more types of agents are used in combination is often conducted.
In recent years, telomerase has become a focus of attention as a cancer molecule target. Telomerase is not expressed in normal cells except for several tissues, but it is reexpressed at a high frequency in 90% or more of cancer cells. The length of telomerase is closely associated with the aging of cells. Accordingly, it is anticipated that such aging of cancer cells is artificially caused by treating them with a telomerase inhibitor. 40% of the agents that are currently used in clinical sites are compounds derived from nature, such as microbial metabolites. Such compounds derived from nature are still widely used as sources for the development of agents.
The present inventors have found that Actinomyces isolated from the soil (the 3533-SV4 strain, belonging to the genus Streptomyces) produces an antitumor compound having multiple oxazole rings (hereinafter referred to as “the GM-95 substance” at times). The inventors have already reported the details thereof (refer to International Publication WO00/24747, for example). The GM-95 substance is the strongest telomerase inhibitor among telomerase inhibitors including synthetic compounds that have been reported to date. The action of the GM-95 substance on several types of cancer cells was analyzed. As a result, it was found that the GM-95 substance induces the aging of cells, which is attended with telomere shorting. In addition, the aged cells had lost their tumorigenicity. These results suggested the possible use of the GM-95 substance as an antitumor agent.
However, nothing has been known regarding an antitumor pharmaceutical in which a telomerase inhibitor such as the GM-95 substance and another antitumor substance are used in combination, or regarding the effects obtained from such combined use.
(Patent Document 1) International Publication WO00/24747